Blood collection and anticoagulation as pre-analytical factors differentially affecting MMP-9 measurement

As part of the complex network involved in extracellular matrix remodeling, matrix metalloproteinase (MMP-) 9 plays a role in central physiological processes including growth and development, angiogenesis, and wound healing (amongst others). In turn, dysregulation of the expression, secretion, activation, or inhibition of MMP-9 may result in the onset and progression of various diseases. Therefore, MMP-9 is regarded as a suitable diagnostic or prognostic biomarker. As a base for reasonable treatment decisions, however, reliable information on MMP-9 levels in the blood have to be obtained, which places high demands on validity, accuracy, and reproducibility of the MMP-9 detection as well as the pre-analytical processing of the respective sample. Thus, selection and correct application of suitable blood collection tubes are of decisive importance. In this Mini-Review, we will address the importance (and limitations) of MMP-9 as a biomarker and focus on confounding effects that may occur in the course of blood withdrawal. Relevant aspects potentially affecting the accurate measurement of MMP-9 in blood samples will be discussed, including the use of serum vs. plasma samples, different anticoagulants present in blood collection tubes, the impact of known contaminants, and the role of major blood cells. Moreover, the cellular and molecular mechanisms underlying these confounding effects will be revisited.